My research plan is to develop and utilize a well defined system for the pharmacological and biochemical study of dopaminergic mechanisms and the neuroleptic agents that are thought to act primarily on such systems. While the dopaminergic inputs in the central nervous system (CNS) have been extensively mapped, thus far no cell type postsynaptic to these inputs has been specified. We propose to identify this post synaptic cell type in the olfactory tubercle of the rat. The olfactory tubercle, a part of the limbic cortex, is particularly suited to such studies becuase of its rich dopamine and dopamine-sensitive adenylate cyclase (DSAC) content and the laminar organization of its neuronal elements. We will use DSAC as a biochemically defined dopamine receptor. We intend to identify the cell type containing the DSAC by the use of lesioning methods in combination with biochemical assays and electron microscopy. Radiofrequency lesions can destroy the dopaminergic tract that ascends to the tubercle and permit us to deduce a pre- or postsynaptic localization for the enzyme. Kainic acid injected directly into the tubercle will destroy intrinsic neuronal cell bodies and should permit a positive identification of the cells that contain the DSAC activity. We will then measure in-vivo levels of cyclic AMP in this cell type in the presence and absence of added dopamine. We will inject dopamine directly into the tubercle and measure changes in cyclic AMP levels after microwave killing. We can measure cyclic AMP levels in the separate cell layers of the tubercle by freezing the tissue and sectioning it before assaying. This system will permit us to: a) obtain evidence about the ability of dopamine to increase cyclic AMP levels in vivo and the ability of neuroleptics to block this increase; b) examine biochemically the effects of acute and chronic neuroleptic treatment upon dopaminergic function. Our long-term objectives are the development of more effective drugs for the treatment of psychosis, and insight into its organic pathology.